Early Complications

REJECTION Acute rejection is common and may occur three to six times in the first postoperative year. After the first year, the frequency of acute rejection is decreased, but rejection can still be seen several years after transplant. Early after transplant, the diagnosis of rejection is based on clinical parameters. Signs of rejection include cough, chest tightness, fever (>0.5°C above baseline), hypoxemia, decline in FEV 1 (>10%), and the development of infiltrate on the chest radiograph. Radiographic abnormalities are less common more than 6 weeks posttransplant, and an acute rejection episode may actually be "radiographically silent" after this time period. Clinically, acute rejection may be difficult to distinguish from infection. Therefore, bronchoscopy with transbronchial biopsy is frequently necessary to make the definitive diagnosis. During episodes of acute rejection in patients with single-lung transplants, there is a proportional decrease in blood flow to the transplanted lung, which can be monitored with radionucleotide perfusion scans.

Acute rejection is treated with large doses of intravenous methylprednisolone, 500 to 1000 mg on day 1, followed by 500 mg IV qd for 2 days. Clinical response is gauged by improvements in oxygenation, spirometry and radiographic appearance and can be expected to occur within 24 to 48 h after treatment is initiated. Failure to do so should suggest infection as an alternative diagnosis. Following clinical improvement, the maintenance dose of prednisone is increased, with a slow taper back to baseline.

INFECTION Infectious complications are the most common cause of morbidity and mortality in lung transplant patients. Infections may be due to bacteria, fungi, or viruses and most commonly affect the allograft. Bacterial pneumonia is the most common complication in the first 3 months after transplant due to decreased mucociliary clearance, diminished cough reflex, disrupted lymphatics, reperfusion injury, and immunosuppression. Late or recurrent infections are associated with an increased risk of developing obliterative bronchiolitis. Besides airborne transmission, a common route of transmission is from the donor lung. The vast majority of washings from a donor before retrieval will grow at least one organism. Perioperative antibiotics based on culture and sensitivity results have decreased the rate of invasive infection significantly. Infection with panresistant Pseudomonas sp. or B. cepacia is associated with increased morbidity and mortality and is generally associated with a higher risk of obliterative bronchiolitis. P. carinii pneumonia is now rare due to common prophylaxis with TMP-SMX. Other commonly encountered infectious agents include gram-negative and gram-positive bacteria, Mycobacterium sp., Aspergillus, CMV, HSV, and Epstein-Barr virus (EBV).

CMV is the most commonly encountered viral agent implicated in posttransplant pulmonary infection. Its clinical spectrum is broad, ranging from asymptomatic shedding to CMV pneumonitis. The risk of infection is directly related to the donor's and recipient's pretransplant immune status. Donor-positive, recipient-negative status is universally associated with the development of CMV infection in the recipient unless aggressive prophylaxis is undertaken with ganciclovir, acyclovir, and intravenous immunoglobulin. If the recipient is CMV-positive, a regimen of ganciclovir followed by acyclovir is used. If the donor and recipient are CMV-negative and either the donor or recipient is HSV-positive, acyclovir only is used. CMV matching has not altered long-term outcome in lung transplant patients, so most centers will transplant regardless of CMV status.

CMV infections occur most commonly between 14 to 100 days posttransplant and manifest as anything from a flulike syndrome to severe multisystem disease including pneumonitis, hepatitis, bone marrow suppression, gastritis, and colitis. Key laboratory features include neutropenia with or without thrombocytopenia, conversion of anti-CMV IgM to positive, and positive CMV cultures from urine, buffy coat, or bronchoalveolar lavage. Definitive diagnosis of CMV pneumonitis requires histopathologic confirmation of tissue obtained by transbronchial biopsy. After confirmation of diagnosis, treatment with ganciclovir or foscarnet is indicated. CMV pneumonitis may be complicated by acute rejection or by bacterial or fungal pneumonia.

Other viral agents, particularly HSV and EBV, have been implicated in posttransplant infections. HSV has a similar presentation to CMV, with diagnosis based on viral culture and differential staining of biopsy specimens. Treatment is with acyclovir. EBV may present as a mononucleosis-type syndrome but is also associated with the development of posttransplant lymphomas.

Fungal infections are less common, but carry a relatively high risk of associated morbidity and mortality. Candida albicans is a common airway colonizer but a much less common pathogen. Systemic candidiasis is usually associated with prolonged courses of broad-spectrum antibiotics. The treatment for C. albicans is fluconazole, but other Candida species may require treatment with amphotericin B. Aspergillus sp. may also colonize the airways; this does not require treatment unless associated with invasive disease, evidenced by ulcerations, or histologic evidence of invasion. Itraconazole with amphotericin B is frequently successful in treating early infections, but disseminated disease is usually fatal.

Lung transplant patients are subject to bacterial endocarditis because during the transplant operation the donor pulmonary veins are attached to the atrium by the establishment of a cuff. Therefore, antimicrobial prophylaxis is necessary before dental and other invasive procedures.

OTHER PULMONARY COMPLICATIONS Airway dehiscence and stenosis are now uncommon postoperative complications. Airway dehiscensce, if it occurs at all, is likely to appear within 3 weeks of transplantation, while the patient is still in the hospital. It can be managed expectantly if an omental wrap was used and the omentum is intact. Bronchial stenosis can occur, limiting clearance of secretions and leading to pneumonia. Treatment is with stenting or laser therapy. Spontaneous pneumothorax necessitates the placement of a thoracostomy tube and evaluation of the airways by bronchoscopy.

MEDICATION EFFECTS Various induction agents are used in the perioperative and immediate postoperative period. These include high-dose corticosteroids and T-cell lytic therapy with equine-derived antithymocyte globulin (ATGAM), a polyclonal thymocyte preparation, or OKT-3, a murine monoclonal antibody. The most common posttransplant immunosuppressives include cyclosporine, azathioprine, and prednisone. Major side effects of these medications are summarized in Table 66-2.

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